Lipase-catalyzed synthesis of precursor dipeptides of RGD in aqueous water-miscible organic solvents

PPL-catalyzed synthesis of the precursor dipeptides of RGD as a cellular adhesion factor, Benzyl-Arg-Gly-NH₂ and CBZ-Gly-Asp-NH₂, was conducted in water-organic cosolvents systems. Five water-miscible organic solvents, which have some advantage over the water-immiscible organic solvent systems or the anhydrous organic solvent systems used often in protease-catalyzed synthesis of a peptide bond, were tested. The reaction condition of PPL-catalyzed synthesis of the dipeptides was optimized by examining the main factors affecting the product yield. The optimal reaction condition for the synthesis of Benzyl-Arg-Gly-NH₂ was set up as pH 8.0, 15°C in 40% MeOH for 10 h with the maximum yield of 73.6%. The optimum condition for the synthesis of CBZ-Gly-Asp-NH₂ was pH 7.0, 15°C in 50% MeOH for 10h with the maximum yield of 67.0%.